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Biomedical subjects

S R Wilson

Publications and source records attributed to S R Wilson.

At least 73 records · Page 4Linked to original sources

On extending the transmission/disequilibrium test (TDT).

The transmission/disequilibrium test (TDT), for evaluation of the null hypothesis of neither linkage nor association between a marker locus and disease, is extended to the more general situation of transmission of two multi-allele marker loci from parents to affected offspring. Transmission probabilities are derived for a generalized single locus disease model, where the disease locus is taken to lie between the two marker loci. There could be unlinked modifier loci for the disease. Examples of the extended TDT are given and it is shown how the contribution from each locus can be evaluated, both separately and jointly.

Chromosome Mapping↗

Respiratory effects associated with indoor nitrogen dioxide exposure in children.

BACKGROUND: The human health effects of exposure to indoor nitrogen dioxide (NO2) are unclear, and few studies have examined the effects of short-term peak levels of exposure. METHODS: The association between indoor exposure to NO2 and respiratory illness was examined in 388 children aged 6-11 years. The NO2 levels were monitored during winter in 41 classrooms, from four schools with unflued gas heating and four schools with electric heating. Each classroom was monitored daily with 6-hour passive diffusion badge monitors over nine alternate weeks, and with hourly monitors over two of those weeks. Children living in homes with unflued gas appliances were also monitored daily over four evenings during times of gas use. RESULTS: Exposure to NO2 at hourly peak levels of the order of > or = 80 ppb, compared with background levels of 20 ppb, was associated with a significant increase in sore throat, colds and absences from school. An increase in cough with phlegm was marginally significant. Significant dose-response relationships were demonstrated for these four measures with increasing levels of NO2 exposure. CONCLUSIONS: Short-term peak levels of exposure are important to consider in relation to adverse respiratory effects associated with NO2 exposure.

Air Pollution, Indoor↗

The partition matrix: exploring variable phylogenetic signals along nucleotide sequence alignments.

The partition matrix is a graphical tool for comparative analysis of nucleotide sequences following alignment. It is particularly useful for investigating the divergent phylogenies of sequence regions undergoing reticulate evolution. A partition matrix is generated by determining the consistency of the parsimoniously informative sites in a set of aligned sequences with the binary partitions inferred from the sequences. Since the linear order of sites is maintained, the matrix can be used to assess whether the distribution of sites either supporting or conflicting with particular partitions changes along the length of the alignment. The usefulness of the matrix in allowing visual identification of differences in evolutionary history among regions depends on the order in which partitions are shown; several suitable ordering schemes are proposed. We demonstrate the use of the partition matrix in interpreting the evolution of the pseudoautosomal boundary region on the sex chromosome of catarrhine primates. Its routine use should help to avoid attempts to derive single phylogenies from sequences whose evolution has been reticulate and to identify the gene conversion or recombination events underlying the reticulation. The method is relatively fast. It is exploratory, and it can form the basis for more formal analysis, which we discuss.

Animals↗

Introduction of an ultrasound picture archiving and communication system: experience in the first year.

OBJECTIVE: To describe the authors' first year's experience with a picture archiving and communication system (PACS) for the management and storage of ultrasound images and to discuss the financial impact of the system in terms of costs of purchase, installation and operation. MATERIALS AND METHODS: The Toronto Hospital, General Division, performs more than 30000 ultrasound studies each year. On June 27, 1994, an Ultra PACS (ALI Technology Incorporated, Richmond, BC) was introduced as the only method of image storage and archiving in the Ultrasound Division. RESULTS: After structural renovations and a detailed work flow analysis, the Ultrasound Division converted from film to the PACS over a single weekend with no back-up. The advantages to date include consistently high-quality images; rapid image retrieval (images from the same day [online], 0 to 45 seconds; archived images [online], 3 to 5 minutes; images in storage [offline], 3 minutes); no loss of images; more efficient patient through-put, which allows the division to handle the same number of patients in 20% less operational time (change from a 10-hour day to an 8-hour day, over a 5-day week); less end-of-day overtime; and an improved work environment. There has been no change in the division's complement of full-time equivalent technologists, the number of film librarians has been reduced by 1, and physician service time has decreased by 20%. There has been no significant impact on overall operational financial status. CONCLUSION: The PACS has proved an efficient method for managing large numbers of ultrasound images in a cost-effective and technically sound manner. Its installation provides the basis for meeting the Ultrasound Division's next objective, to eliminate paper as the primary method of managing patient information and reports.

Computer Communication Networks↗

Biological applications of fullerenes.

Thus far, development of applications of fullerenes in biology has been hampered by the poor water solubility of fullerenes. In spite of such concerns, fullerenes have proved useful for a wide variety of biological applications. As derivatized and underivatized fullerenes continue to become increasingly available, additional applications and further development of those discussed in this article will invariably follow.

Animals↗

Patients' perceptions compared with objective ratings of asthma severity.

BACKGROUND: Optimal asthma management requires accurate assessment of asthma severity. OBJECTIVE: To compare patients' perceptions of their asthma severity with that obtained by using the guidelines published by the National Asthma Education and Prevention Program's Expert Panel and with functional impairment measured by spirometry and numeric criteria of the American Thoracic Society. METHODS: We enrolled 323 patients age 18 to 50 years who were members of the Kaiser Foundation Health Plan for > or = 1 year in a randomized control trial of an asthma education program. Each had a confirmed diagnosis of bronchial asthma and had been receiving antiasthma medication for > or = 1 year. Patients rated the severity of their asthma. Office spirometry was performed, and, using the Mini-Wright peak flow meter, patients kept 2-week diaries of at-home recordings of morning and evening peak expiratory flow rates. RESULTS: A statistically significant association was noted between patients' perceptions of asthma severity and both medication severity rating (P < .001) and diurnal variation rating (P = .003) and evening peak expiratory flow rate percentage (P = .019). In comparison with a severity composite based on criteria of the National Asthma Education Program, 54% of patients accurately estimated asthma severity, 27% overestimated, and 20% underestimated severity. CONCLUSION: A clinically significant proportion of asthmatic patients substantially underestimate disease severity and thereby may be at risk of increased mortality or morbidity.

Adolescent↗

Lipiodol accumulation in hepatic hemangioma. Detection with osmium postfixation.

Lipiodol has been used to increase the detectability of small primary neoplasms in the liver. We report a patient who was found to have lipiodol deposits in the liver one month after intra-arterial injection. The region was resected, under ultrasound control, because of the impression that the lesion was malignant. The specimen contained two small hemangiomas as well as many small dysplastic nodules (adenomatous hyperplasia) in a noncirrhotic parenchyma. To locate the lipiodol deposit in this case, the tissue was radiographed, postfixed in osmium tetroxide, and embedded in paraffin. Black osmium-stained deposits were found within the cavities of the hemangiomas but not in the dysplastic nodules. Most of the deposits were extracellular multivesiculated bodies with a small focus of lipid droplets engulfed by multinucleated foreign-body type giant cells. This report reinforces that hepatic lipiodol retention is not specific for hepatocellular carcinoma. We present, for the first time, the histologic appearance of lipiodol accumulation in an hemangioma. The value of osmium tetroxide postfixation for the detection of lipiodol is also demonstrated.

Adult↗

Intraoperative end-tidal carbon dioxide levels and derived calculations correlated with outcome in trauma patients.

BACKGROUND: To determine the relationship between the prognosis of seriously injured patients requiring emergency surgery and intraoperative end-tidal CO2 variables and "excess Pco2." METHOD: Retrospective chart review of 100 seriously injured patients admitted to Detroit Receiving Hospital and requiring major surgery (mortality rate of 40%). Standard intraoperative monitoring, including continuous capnography, plus arterial blood analyses every 15 to 30 minutes during surgery. RESULTS: After resuscitation for 45 to 90 minutes, 11 patients had a systolic blood pressure < 100 mm Hg and, of these patients, 10 (91%) died. Of the remaining 89 patients, mortality rates were 53% (16/30), with an end-tidal CO2 of 22 mm Hg or less, versus 24% (14/59) with an end-tidal CO2 of 23 mm Hg or more (p = 0.011). An arterial to end-tidal Pco2 difference of 13 mm Hg or more after resuscitation was associated with an increased mortality rate (50% (20/34 vs. 18% (20/55)) (p < 0.005). The mortality rate was particularly high, with a final arterial to end-tidal Pco2 difference of 12 mm Hg or more (73% (30/41) versus 17% (10/59) (p < 0.001). A final Paco2 excess (i.e., the amount by which the Paco2 was higher than expected from the bicarbonate) > 1.0 mm Hg was also associated with an increased mortality rate ((62% (33/53) vs. 15% (7/47)) (p < 0.001). CONCLUSION: Values derived from the end-tidal CO2 and the excess Pco2 should be monitored intraoperatively in critically injured patients. Efforts should be made to improve cardiac output and adjust ventilation to maintain an end-tidal Pco2 of 25 mm Hg or more, an arterial to end-tidal CO2 difference of 12 mm Hg or less, and an excess Paco2 of 1.0 mm Hg or less.

Adult↗

Manifestations of Crohn disease at US.

Crohn disease is a chronic inflammatory disorder of the intestines that is characterized by multiple episodes of exacerbation and remission. Although barium studies and endoscopy remain the most valuable tools for assessment of mucosal and luminal changes, sonography has proved to be a safe and noninvasive modality for characterization of mural and perienteric changes. Ultrasonography (US) can accurately demonstrate the classic features of Crohn disease as well as the complications frequently associated with the disease. The addition of color Doppler imaging may allow differentiation of chronic from active bowel wall thickening. In expert hands, US appears to be a sensitive modality for preliminary investigation of patients with symptomatic Crohn disease. US can also be used to assess the response to treatment and to detect postoperative recurrence. Finally, US enables accurate selection of patients in whom the possibility of surgery or percutaneous intervention would justify other means of investigation, particularly computed tomography.

Appendicitis↗

An education program for parents of children with asthma: differences in attendance between smoking and nonsmoking parents.

We studied smoking status in relation to parental attendance at an asthma education program for child patients of a health maintenance organization. Nonattendance rates were 24%, 42%, and 78% in nonsmoking, one-smoker, and two-or-more-smoker families, respectively, and 33% overall. Only the number of smokers (odds ratio [OR] = 3.1; 95% confidence interval [CI] = 1.8, 5.3) and perceived adverse impact of asthma on the family (OR = 0.4; 95% CI = 0.2, 0.9) were retained in a multivariate model that correctly classified 73% of families; demographic characteristics, frequency of asthma symptoms, and health care use were rejected. There was a tendency for smoking parents to deny that their child had asthma (17% among families with two or more smokers; 9% among nonsmoking families). Asthma education programs may fail to involve parents who smoke.

Adult↗

Education of parents of infants and very young children with asthma: a developmental evaluation of the Wee Wheezers program.

A randomized control trial of the Wee Wheezers asthma education program was conducted with 76 children < 7 years of age, 31% of whom were on a medication regimen consistent with mild, 51% with moderate, and 18% with moderately severe/severe asthma. Treatment children showed improved morbidity at 3-month follow-up relative to the changes in the controls: increased symptom-free days in the preceding 2 weeks (mean change of +2.2 vs. -2.6 in the controls; p = .004) and month (+2.0 vs. -3.8; p < .02), fewer nights of parental sleep interruption in a typical week (+0.7 vs. +1.8; p < or = .05), and a trend toward fewer asthma sick days (-0.2 vs +0.7; p = ns). These improvements were accompanied by significantly better parental asthma management compared with controls (more consistent use of preventive medications, p < or = .01; early symptom intervention, [corrected] p < or = .05) and trends toward more restrictions on smoking in the home (p < .07) and decreased parental confusion about asthma treatment (p < .11). This study provides evidence that a multisession program of asthma education for parents can improve parental asthma management and clinical outcomes in very young children and provides information on the validity and sensitivity of various asthma outcome measures in this age group.

Asthma↗

Abdominal sonography in asymptomatic executives: prevalence of pathologic findings, potential benefits, and problems.

Abdominal ultrasonography was performed on 1000 asymptomatic executives over a period of 6 months as part of a comprehensive health examination. The use of ultrasonography in these persons was evaluated with regard to the prevalence and variety of pathologic conditions detected as well as potential benefits, risks, and use as a screening tool. Significant sonographic diagnoses included renal cell carcinoma in four patients (0.4%) and abdominal aortic aneurysm in four patients (0.4%). Abdominal sonography performed on 7925 asymptomatic executives over a subsequent 2 1/2 year period led to detection of 23 (0.3%) additional renal cell carcinomas. The prevalence of renal cell carcinoma in this population is substantially greater than that of the general population. Abdominal sonography facilitates detection of occult renal neoplasms and aortic aneurysms. The cost effectiveness and potential use of sonography as a screening tool remains to be determined, however, given the relatively low overall prevalence of these pathologic conditions.

Abdomen↗

Cytochrome P-450scc-mediated oxidation of (20S)-22-thiacholesterol: characterization of mechanism-based inhibition.

(20S)-22-thiacholesterol (1) is found to be a potent competitive inhibitor of pregnenolone biosynthesis from cholesterol by purified reconstituted bovine adrenal cytochrome P-450scc. The apparent dissociation constant Kd, determined from difference spectra, is 0.6 microM, close to the value from kinetic studies for the apparent inhibition constant, Ki, of 0.8 microM. Studies of the time course of pregnenolone production indicate that under turnover conditions the competitive inhibitor (1) is converted to a tighter binding inhibitor, shown to be (20S,22R)-22-thiacholesterol S-oxide (4), with high diastereoselectivity and in a time-dependent manner. Both the diastereomeric sulfoxides, (20S,22S)-22-thiacholesterol S-oxide (3) and (20S,22R)-22-thiacholesterol S-oxide (4), exhibit properties consistent with their being competitive versus cholesterol, but the (22R)-sulfoxide (4) binds approximately 10 times more tightly than the (22S) diastereomer (3). The apparent Kd values of sulfoxides 4 and 3 are 0.1 and 1.14 microM, respectively. EPR and absorption spectroscopic studies of enzyme-inhibitor complexes suggest direct coordination of the oxygen atom of the (22R)-sulfoxide (4) with the catalytic heme center. This implies that the inhibitor operates by directly blocking further reaction at the active site heme group, with a substantial lifetime of the enzyme-inhibitor complex.

Cholesterol↗

Crystal structure of doisynolic acid and the structure of other products formed during its synthesis.

The crystal structure of the D-seco-estrogen doisynolic acid shows it to have the natural S configuration at the position derived from C-14 in estrone. Two major by-products during the synthesis of doisynolic acid from estrone are shown to be dimeric steroids. One is an aldol condensation product, and the other appears to arise from an alkaline cleavage of the aldol product.

Crystallization↗

Prospective study of hospitalization for asthma. A preliminary risk factor model.

We conducted an exploratory analysis of several prospectively obtained objective measures of disease activity to derive a predictive model of hospitalization for asthma among 310 adults, ages 18 to 50 yr, with moderate to severe asthma. Baseline characteristics associated with increased risk of hospitalization in the succeeding year include (1) prior year hospitalization, (2) moderate or severe respiratory impairment, (3) a medication regimen consistent with severe asthma, (4) a history of significant systemic steroid use, (5) maximum overnight PEF variability > 40%, and (6) mean evening PEF < 60% of predicted (relative risk = 6.5, 6.9, 8.1, 3.7, 3.0, and 3.2, respectively). Recursive partitioning analysis, depicted as a "classification tree," provided a more sensitive (94%) and specific (68%) multivariate description of the data set than either logistic regression (87 and 48%, respectively) or a simple additive risk model (46 and 93%, respectively). Patients with very high (> 50%), moderately elevated (10 to 15%), and very low (< 5%) risk of hospitalization were identified on the basis of particular combinations of prior hospitalization history, level of respiratory impairment, and medication regimen. Overnight variability and mean evening PEF measured at home over a 2-wk period proved less informative for risk stratification than respiratory impairment determined once at baseline by office spirometry. The findings warrant replication and extension in other populations with the goal of developing decision rules for risk stratification and effective interventions for risk reduction.

Adult↗